Curcumin exerts therapeutic effects on colorectal cancer by inducing pyroptosis through caspase‑1 activation

Mol Med Rep. 2025 Dec;32(6):327. doi: 10.3892/mmr.2025.13692. Epub 2025 Sep 26.

Abstract

Colorectal cancer (CRC) is a substantial global health challenge, with current treatments often leading to relapse and metastasis. Curcumin, a natural compound derived from turmeric, has shown promise in cancer therapy; however, its mechanisms in CRC are not fully understood. The present study aimed to investigate the role of curcumin in inducing pyroptosis, a form of inflammatory cell death, through caspase‑1 activation in CRC cells. Human CRC cell lines (HCT‑116 and SW480) and normal colon epithelial cells (FHC) were treated with curcumin at varying concentrations. Cell viability, migration and invasion were assessed using Cell Counting Kit‑8, wound healing and Transwell assays, respectively. Pyroptosis was evaluated through lactate dehydrogenase (LDH) release, TUNEL staining and western blot analysis of pyroptosis‑related proteins (caspase‑1, gasdermin D, nucleotide‑binding oligomerization domain‑like receptor protein 3, IL‑1β and IL‑18). The role of caspase‑1 was further examined using the inhibitor VX‑765. Curcumin significantly reduced CRC cell viability, migration and invasion in a dose‑dependent manner. In addition, it induced pyroptosis, as evidenced by cell membrane swelling, increased LDH release and upregulation of pyroptosis‑related proteins. Inhibition of caspase‑1 with VX‑765 attenuated these effects, confirming the role of caspase‑1 in curcumin‑induced pyroptosis. In conclusion, curcumin may exert anti‑CRC effects by inducing caspase‑1‑mediated pyroptosis, highlighting its potential as a therapeutic agent. These findings suggest that curcumin could be integrated into current CRC treatment strategies, particularly in targeting pyroptosis to enhance tumor suppression.

Keywords: CRC; caspase‑1; curcumin; pyroptosis.

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Caspase 1* / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / metabolism
  • Colorectal Neoplasms* / pathology
  • Curcumin* / pharmacology
  • Enzyme Activation / drug effects
  • Gasdermins
  • HCT116 Cells
  • Humans
  • Interleukin-18 / metabolism
  • Interleukin-1beta / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Phosphate-Binding Proteins / metabolism
  • Pyroptosis* / drug effects
  • para-Aminobenzoates / pharmacology

Substances

  • Curcumin
  • Caspase 1
  • Antineoplastic Agents
  • Phosphate-Binding Proteins
  • Interleukin-1beta
  • para-Aminobenzoates
  • Interleukin-18
  • GSDME protein, human
  • GSDMD protein, human
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Gasdermins